Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
  • A61M5/178—Syringes
  • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
  • A61M5/2046—Media being expelled from injector by gas generation, e.g. explosive charge
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
  • A61M5/178—Syringes
  • A61M5/31—Details
  • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
  • A61M5/31565—Administration mechanisms, i.e. constructional features, modes of administering a dose
  • A61M5/3159—Dose expelling manners
  • A61M5/31591—Single dose, i.e. individually set dose administered only once from the same medicament reservoir, e.g. including single stroke limiting means

Definitions

• the present disclosure relates to an injector and a method for injecting a solution using the injector.
• the needle-equipped injector inserting an injection needle into the injection target, pushing a plunger and then injecting the medical liquid, usually slowly, disperses the medical liquid into the injection target, allowing a medicinal effect to be appropriately exhibited.
• a very small amount of the medical liquid is slowly administered (for example, at about 0.0033 ⁇ L/s).
• the medical liquid is "slowly" administered on the basis of the subjectivity of the administrator.
• the needleless injector that utilizes the combustion energy of an ignition agent as ejection energy is capable of delivering a medical liquid to the nucleus or cytosol of a cell by instantly pushing out and administering the medical liquid.
• the needleless injector can deliver active ingredients to the injection target without necessarily requiring viral vectors or lipid carriers, and thus the usefulness of the needleless injector has been attracting attention also from the viewpoint of a drug delivery system (DDS), and application of the needleless injector to delivery of various medical liquids using a low-molecular-weight molecule, a peptide, a protein, an antibody, or the like having an anticancer action has been studied.
• DDS drug delivery system
• Non-Patent Document 1 A medical liquid administered from the skin surface using a needleless injector is delivered intradermally through the stratum corneum of the skin as a jet stream (Non-Patent Document 1). By adjusting the output, it is possible to deliver a medical liquid subcutaneously or intramuscularly (Non-Patent Document 4).
• Patent Document 1 JP 2012-61269 A
• the biofunctional substance is preferably one or more selected from the group consisting of a nucleic acid, a peptide, a protein, and a low-molecular-weight compound.
• nucleic acid examples include deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and peptide nucleic acid (PNA).
• the nucleic acid may be a nucleic acid including a portion encoding a protein, or a nucleic acid not including a portion encoding a protein (non-coding nucleic acid).
• peptides and the proteins include antigens (that is, those that produce antibodies against the peptides and proteins), antibodies, peptide vaccines, protein vaccines, peptide hormones, protein hormones, growth factors, cytokines, blood coagulation factors, serum albumin, digestive enzymes, anti-inflammatory peptides, and anti-inflammatory proteins.
• a low-molecular-weight compound typically refers to a compound having a molecular weight of 2000 or less.
• the low-molecular-weight compound is not limited thereto, and encompasses a compound that can be treated as a low-molecular-weight compound in the industry.
• Examples of a preferable range of the molecular weight of the low-molecular-weight compound include 50 or greater, or 100 or greater. Further examples include 2000 or less and 1000 or less. That is, examples include 50 to 2000, 50 to 1000, and 100 to 2000.
• the biofunctional substance when the biofunctional substance is a nucleic acid containing a portion encoding a protein, an amount of the protein encoded by the nucleic acid can be quantified and used as an index for evaluating the physiological activity. Further, the activity of the protein may be quantitatively evaluated. For example, as illustrated in examples described below, when the protein is luciferase, the physiological activity can be evaluated by measuring an intensity of bioluminescence.
• the nucleic acid may be incorporated into a virus vector or carried by a lipid nanoparticle and contained in the solution.
• high physiological activity can be achieved even when a virus vector or a lipid nanoparticle is not used.
• a virus vector or a lipid nanoparticle is not used, it is possible to reduce the possibility that a side reaction such as anaphylaxis will be induced in the injection target.
• the solution may contain common additives such as a buffer, a tonicity agent, a pH adjuster, an antioxidant, a thickener, a stabilizer, a wetting agent, an emulsifier, and a binder, as necessary.
• common additives such as a buffer, a tonicity agent, a pH adjuster, an antioxidant, a thickener, a stabilizer, a wetting agent, an emulsifier, and a binder, as necessary.
• phosphate-based buffers are preferable from the viewpoint of versatility.
• ionic tonicity agent examples include salts such as sodium chloride, potassium chloride, calcium chloride, and magnesium chloride.
• nonionic tonicity agent examples include glycerin, propylene glycol, polyethylene glycol, glucose, sorbitol, mannitol, trehalose, maltose, and sucrose.
• sodium chloride is preferable from the viewpoint of versatility.
• pH adjuster examples include hydrochloric acid, phosphoric acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium hydrogen carbonate.
• antioxidants examples include ascorbic acid, sodium sulfite, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, and tocopherol.
• thickener examples include alginic acid, polyethylene glycol, hydroxypropylmethyl cellulose, and sodium carboxymethyl cellulose.
• the content of the biofunctional substance in the solution is not particularly limited, and can be adjusted as appropriate by a person skilled in the art within a range in which the biofunctional substance can exhibit physiological activity.
• Examples of the content include 0.0001 mg/mL or higher, 0.001 mg/mL or higher, and 0.01 mg/mL or higher. Further, examples include 1000 mg/mL or less and 100 mg/mL or less. That is, examples include 0.0001 to 1000 mg/mL, 0.001 to 100 mg/mL, and 0.01 to 100mg/mL.
• the injector injects the solution into the injection target by ejecting the solution from the outlet port of the ejection part.
• application of energy by the pressurization part for pressurizing the solution containing the biofunctional substance can adopt a form of energy application based on a known pressurization technique.
• An example of the energy applied may be a chemically-generated energy such as, for example, a combustion energy generated by an oxidation reaction of a low explosive or a high explosive.
• the energy for pressurization may be generated electrically.
• energy caused by a piezoelectric element or an electromagnetic actuator driven by applied electric power may be employed.
• the energy for pressurization may be generated physically.
• elastic energy of an elastic body or internal energy of a compressed body, such as compressed gas may be employed.
• the energy for pressurization may be any energy as long as the energy enables ejection of the solution with the injector. Further, the energy for pressurizing the solution may be a composite-type energy obtained by appropriately combining the above-described combustion energy, energy generated by electric power, and internal energy such as elastic energy.
• the pressurization part may perform pressurization by utilizing pressure generated by combustion of the explosive ignited by the ignition device, or may perform pressurization by utilizing pressure generated when the compressed gas is released. Further, the pressurization part may apply pressure by utilizing a biasing force of a compression spring, or may apply pressure by utilizing an electromagnetic force such as, for example, a linear electromagnetic actuator.
• the pressurization part preferably utilizes at least the pressure generated by the combustion of the explosive ignited by the ignition device, and may be used in combination with any of the other pressurization modes described above.
• the explosive used may be, for example, any one of an explosive containing zirconium and potassium perchlorate (ZPP), an explosive containing titanium hydride and potassium perchlorate (THPP), an explosive containing titanium and potassium perchlorate (TiPP), an explosive containing aluminum and potassium perchlorate (APP), an explosive containing aluminum and bismuth oxide (ABO), an explosive containing aluminum and molybdenum oxide (AMO), an explosive containing aluminum and copper oxide (ACO), and an explosive containing aluminum and iron oxide (AFO), or an explosive composed of two or more of these explosives in combination.
• ZPP zirconium and potassium perchlorate
• THPP titanium hydride and potassium perchlorate
• TiPP titanium and potassium perchlorate
• APP explosive containing aluminum and potassium perchlorate
• ABO aluminum and bismuth oxide
• AMO aluminum and molybdenum oxide
• ACO explosive containing aluminum and copper oxide
• AFO aluminum and iron oxide
• the pressurization part utilizes energy generated by combustion of a gas generating agent as ejection energy
• a single base smokeless explosive (GG) and various types of gas generating agents used in a gas generator for an air bag and a gas generator for a seat belt pretensioner may be used as the gas generating agent.
• the jet injector 1 includes a container 11, a container holder 12, an actuator 13, and a casing 14, which are integrally assembled to form an assembly.
• An ejection port denoted by reference sign 11c is formed at a tip end of the jet injector 1.
• the jet injector 1 pressurizes the solution containing the biofunctional substance (hereinafter, also simply referred to as a "solution") utilizing the combustion energy of an explosive, thereby ejecting the solution from the ejection port 11c.
• the jet injector 1 according to the present embodiment is configured as a needleless injector capable of injection by itself without using an injection needle. However, the jet injector 1 need not be a needleless injector.
• the casing 14 is a tubular member accommodating the actuator 13.
• An ignition device 131 (described below) of the actuator 13 is fitted into the base end side of the casing 14, and the container holder 12 is fitted into the tip end side of the casing 14.
• a threaded part 14a for coupling the casing 14 and the container holder 12 is formed on an inner circumferential surface of the tip end side of the casing 14. The container holder 12 and the actuator 13 are coupled via the casing 14.
• the container 11 includes a main body part 111 and a nozzle part 112 having a diameter smaller than that of the main body part 111, and is formed in a tubular shape. Further, inside the container 11 are formed an accommodating space 11a that is a space capable of accommodating the solution containing the biofunctional substance, and a flow path 11b that communicates with the accommodating space 11a and opens on the tip end side. More specifically, the accommodating space 11a is formed inside the main body part 111, and the flow path 11b is formed inside the nozzle part 112.
• the accommodating space 11a is an example of an accommodation part according to the present disclosure.
• An opening of the flow path 11b is formed in a tip end surface of the nozzle part 112, and the opening serves as the ejection port 11c of the jet injector 1. That is, the jet injector 1 ejects the solution from the ejection port 11c formed in the tip end surface of the nozzle part 112.
• an inner diameter of the flow path 11b of the container 11 is smaller than an inner diameter of the accommodating space 11a.
• a threaded part 111a for coupling the container 11 and the container holder 12 is formed on an outer circumferential surface of the main body part 111.
• the ignition device 131 includes an initiator 1311 and a holding member 1312.
• the initiator 1311 serves as a drive source of the actuator 13 and generates energy for pressurization and ejection of the solution by the injector 100.
• the initiator 1311 is configured as an electric igniter that releases a combustion product by burning an ignition agent accommodated in an interior thereof.
• the holding member 1312 is formed by injection molding of a resin. The injection molding can be performed by a known method. Further, for the holding member 1312, a resin material similar to that of the container 11 can be used.
• the ignition device 131 is configured as an igniter assembly in which the initiator 1311 is fixed to a base end portion of the casing 14 via the holding member 1312, and is fitted into the casing 14, closing the base end portion of the casing 14.
• the ignition device 131 is disposed in the casing 14 with the initiator 1311 facing a base end surface (end surface on the base end side) of the piston 132, and thus the combustion energy of the ignition agent by the initiator 1311 and the combustion energy of a gas generating agent 10 described below are transmitted to the base end surface.
• the jet injector 1 need not include the gas generating agent 10 and may pressurize the solution by utilizing only the combustion energy of the ignition agent by the initiator 1311.
• the gas generating agent and the like to be used as necessary are also included in the pressurization part.
• the piston 132 is disposed on the tip end side of the casing 14, facilitating sliding inside the casing 14 by being pressurized by actuation of the initiator 1311.
• the piston 132 is formed of a metal, and an O-ring or the like may be disposed on a portion thereof to enhance sealing with a sliding surface (that is, inner circumferential surface of the casing 14) on which the piston 132 slides.
• the piston 132 may be formed of a resin and, in such a case, a metal may be used in combination for a portion requiring heat resistance and pressure resistance.
• the plunger 133 is a member that receives the combustion energy of the ignition agent by the initiator 1311 and the combustion energy of the gas generating agent via the piston 132, thereby pressurizing the solution accommodated in the accommodating space 11a.
• the plunger 133 is accommodated in the casing 14 and disposed between the piston 132 and the nozzle part 112 of the container 11.
• the plunger 133 is formed in a rod shape, and a base end portion thereof is engaged with a tip end portion of the piston 132. Further, a tip end portion of the plunger 133 is inserted into the main body part 111 of the container 11, and the accommodating space 11a is defined by the plunger 133 and the main body part 111.
• the plunger 133 is slidable inside the main body part 111 and, with the sliding of the plunger 133, the solution accommodated in the accommodating space 11a is pressurized, passes through the flow path 11b, and is ejected from the ejection port 11c.
• the plunger 133 is formed of a material that smoothly slides against the main body part 111 of the container 11 and prevents the solution from leaking from the plunger 133 side.
• the material of the plunger 133 include butyl rubber and silicone rubber. Further, for the purpose of securing and adjusting slidability between the plunger 133 and the main body part 111 of the container 11, an outer circumferential surface of plunger 133 and the inner circumferential surface of the main body part 111 may be subjected to coating or surface finishing with various substances.
• a contour of a tip end portion of the plunger 133 is formed in a shape substantially coinciding with a contour of a tip end portion of the accommodating space 11a.
• the housing 2 illustrated in FIG. 1 is a member that accommodates the jet injector 1 and functions as a grip part that a user grasps to use the injector 100.
• a battery 3 for supplying a drive current to the actuator 13 (more specifically, the initiator 1311) of the jet injector 1 is provided inside the housing 2.
• an outer surface of the housing 2 is provided with a plurality of switches 21 for operating the jet injector 1 to achieve ejection of the solution.
• an inner surface of the housing 2 is provided with a socket (not illustrated) connected to the initiator 1311 of the jet injector 1.
• Power from the battery 3 to the jet injector 1 is supplied between an electrode on the housing 2 side and an electrode on the initiator 1311 side of the jet injector 1 via wiring by a press operation of the switch 21 by the user. Further, a control unit (not illustrated) such as a microcomputer is provided inside the housing 2. The control unit controls supply of an ignition current to the initiator 1311 of the jet injector 1 on the basis of a signal from each switch, thereby performing operation control of the jet injector 1.
• the power for actuating the initiator 1311 is supplied from the battery built into the housing 2.
• the power may be supplied from the outside via a power cable.
• the injection needle 4 is attached to the nozzle part 112 of the jet injector 1 and includes a base section 41 and a needle tube 42.
• the injection needle 4 is an example of an "ejection part" according to the present disclosure, and is configured to facilitate inflow of the solution pressurized by the actuator 13 of the jet injector 1 and ejection of the flowing solution to the injection target.
• the base section 41 is formed in a tubular shape. More specifically, as illustrated in FIG. 2 , the base section 41 includes a base body 411 having a tubular shape and a flange part 412 formed at a base end portion of the base body 411 and protruding outward in a radial direction.
• the nozzle part 112 of the jet injector 1 is press-fitted into an opening on the base end side of the base body 411. Accordingly, the opening on the base end side of the base body 411 is configured as an inlet port 4a through which the solution containing the biofunctional substance can flow from the accommodating space 11a of the container 11 into the injection needle 4.
• the base section 41 can be formed of, for example, a resin material.
• a resin material a known synthetic resin such as polycarbonate, polypropylene, or polyethylene, for example, can be adopted.
• the base section 41 may be made of a metal. Examples of the metal material forming the base section 41 include stainless steel, aluminum, an aluminum alloy, titanium, and a titanium alloy.
• the material of the base section 41 is not particularly limited, but in consideration of suppression of pressure loss of the solution flowing into the injection needle 4, a material having relatively high rigidity such as stainless steel is preferably used for the base section 41.
• the needle tube 42 is inserted into the injection target and ejects the solution containing the biofunctional substance into the injection target.
• a base end portion of the needle tube 42 is connected to a tip end of the base section 41, and an internal space of the base section 41 and an internal space of the needle tube 42 communicate with each other. Accordingly, an opening on the tip end side of the needle tube 42 is configured as the outlet port 4b through which the solution containing the biofunctional substance flowing into the injection needle 4 from the inlet port 4a can be ejected to the injection target.
• a sharp needle tip that punctures the skin is formed at a tip end portion of the needle tube 42, facilitating insertion of the needle tube 42 into the injection target.
• a material of the needle tube 42 is not particularly limited, but examples thereof include stainless steel. Further, as a metal material other than stainless steel, aluminum, an aluminum alloy, titanium, a titanium alloy, or the like can be adopted. Further, the needle tube 42 may be formed of a resin material.
• a flow path 4c from the inlet port 4a to the outlet port 4b is formed by the internal space of the base section 41 and the internal space of the needle tube 42.
• the solution flowing into the injection needle 4 from the inlet port 4a flows through the flow path 4c, reaches the outlet port 4b, and is ejected from the outlet port 4b to the injection target.
• a material of the fixing jig 5 is not particularly limited, but the fixing jig 5 can be formed of a metal material such as stainless steel, copper, aluminum, iron, titanium, or a titanium alloy, for example, as with the container holder 12. Further, for example, the fixing jig 5 may be formed of a resin material such as polycarbonate, polypropylene, or polyethylene.
• the injection of the solution into the injection target by the injector 100 is performed by operating the injector 100 with the needle tube 42 of the injection needle 4 being inserted into the injection target.
• the operation of the injector 100 will be described below.
• the solution containing the biofunctional substance may be accommodated in the accommodating space 11a of the container 11 from the start, or may be accommodated in the accommodating space 11a by suctioning the solution from outside the injector 100 through the outlet port 4b of the injection needle 4.
• the solution containing the biofunctional substance is accommodated in the accommodating space 11a of the container 11 from the start, making it possible to reduce medical liquid leakage and dead volumes.
• the drive current is supplied to the actuator 13 of the jet injector 1 (more specifically, the initiator 1311) by operation of the switches 21 by the user and the actuator 13 is actuated, the combustion product of the ignition agent is released from the initiator 1311 to the combustion chamber 15.
• the gas generating agent 10 disposed in the combustion chamber 15 is burned by the combustion product of the ignition agent, generating gas in the combustion chamber 15.
• the base end surface of the piston 132 is exposed to the combustion chamber 15. Therefore, when the actuator 13 is actuated, the piston 132 receiving the combustion energy (pressure) of the ignition agent or the gas generating agent at the base end surface slides toward the tip end side of the casing 14.
• the plunger 133 is pushed toward the tip end side of the accommodating space 11a by the piston 132, and the solution in the accommodating space 11a is pressurized.
• the solution passes through the flow path 11b from the accommodating space 11a and is ejected from the ejection port 11c formed in the nozzle part 112.
• the solution ejected from the ejection port 11c of the nozzle part 112 flows into the injection needle 4 through the inlet port 4a of the injection needle 4 attached to the nozzle part 112.
• the solution flows through the flow path 4c and is ejected from the outlet port 4b to the injection target. As described above, the operation of the injector 100 is completed.
• FIG. 3 is an overall view of an injector 100A according to a modified example of the present embodiment.
• FIG. 3 illustrates an external appearance of the injector 100A.
• FIG. 4 is a cross-sectional view of the injector 100A.
• the housing 2 of the injector 100A is provided with a power cable 6 for supplying a drive current to the actuator 13 of the jet injector 1.
• the actuator 13 of the jet injector 1 according to the modified example includes a body 134 having a tubular shape that accommodates the ignition device 131 and the piston 132.
• the ignition device 131 is disposed on the base end side and the piston 132 is disposed on the tip end side of the body 134.
• the combustion chamber 15 is formed between the ignition device 131 and the piston 132 in an internal space of the body 134.
• the injector according to the present disclosure can also be implemented with a configuration such as that of the injector 100A.
• the ejection rate is less than or equal to the upper limit described above, it is possible to suppress damage to cells and tissues.
• the entire organ was collected as one specimen and cryopreserved at -80°C.
• the epididymal head and tail associated with the testis were each carefully separated from the testis and cryopreserved.
• these are referred to as a 35/40 group, a 55/40 group, and a 75/40 group, respectively.
• the lower limbs were collected 24 hours after administration, and the Luc activity in the knee joint was measured. The results comparing the means + SD are shown in FIG. 7 .
• the ejection rates were measured using the 30G-pNFI-25/40, the 30G-pNFI-35/40, the 30G-pNFI-55/40, the 30G-pNFI-75/40, and the pNFI-35/40.
• the tip end of the injector was immersed in PBS, and 30 ⁇ L of 1% malachite green solution was ejected.
• the time required from the start to the end of ejection was measured by high-speed camera analysis, and each ejection rate was calculated by dividing 30 ⁇ L by this time period. The results are shown in FIG. 8 .
• the ejection rates of the needle-equipped 30G-pNFI were significantly higher than the maximum speed of the syringe pump (83.3 ⁇ L/s) under all conditions, measuring 398.4 ⁇ L/s or higher. Further, the ejection rate increased in a ZPP dose-dependent manner.
• Each spleen was collected 24 hours after administration, and the Luc activity was measured. The results comparing the means + SD are shown in FIG. 9 .
• the Luc activity increased in a dose-dependent manner. Further, when the same amount of pLuc was administered using the 30G-pNFI-35/40, the Luc activity increased about three-fold as compared with that when the 30G injection needle-equipped insulin syringe was used.
• the Luc activity of the 1 mg/mL administration group was 3.6 times higher than that of the 0.3 mg/mL administration group, while the Luc activity of the 3 mg/mL administration group was about the same as that of the 1 mg/mL administration group.
• a similar trend was recognized when using the 30G needle-equipped Hamilton syringe (30G-Syr/pump).
• the 30G-pNFI-35/40 and the 30G needle-equipped Hamilton syringe having the same pLuc concentrations were compared, the 30G-pNFI-35/40 showed approximately 50 times higher Luc activity than those of the 30G needle-equipped Hamilton syringe across all pLuc concentrations.
• Each spleen was collected 24 hours after administration, and the Luc activity was measured. The results comparing the means + SD are shown in FIG. 11 .
• 24 hours after administration the testis, the epididymal head, and the epididymal tail were collected, and the Luc activity was measured.
• the results comparing the means + SD of the Luc activity in the testis, the epididymal head, and the epididymal tail are shown in FIGS. 12 , 13 and 14 , respectively.
• the RFU values in the testis were 3.0 + 1.2 ⁇ 10 5 and 8.2 ⁇ 1.9 ⁇ 10 5 , respectively.
• the RFU values in the testis were 6.1 ⁇ 3.7 ⁇ 10 7 and 7.3 ⁇ 3.6 ⁇ 10 7 respectively, showing similar levels.
• the Luc activity increased in the following order: administration using the 30G needle-equipped Hamilton syringe at an administration rate of 1 ⁇ L/s, administration using the 30G needle-equipped Hamilton syringe at an administration rate of 10 ⁇ L/s, and administration using the 30G-pNFI-25/40. From these results, the Luc activity is considered to increase in an administration rate dependent manner.

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• Health & Medical Sciences (AREA)
• Vascular Medicine (AREA)
• Engineering & Computer Science (AREA)
• Anesthesiology (AREA)
• Biomedical Technology (AREA)
• Heart & Thoracic Surgery (AREA)
• Hematology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Infusion, Injection, And Reservoir Apparatuses (AREA)

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• 2023
  • 2023-08-30 EP EP23865285.3A patent/EP4588495A1/fr active Pending
  • 2023-08-30 WO PCT/JP2023/031451 patent/WO2024057929A1/fr not_active Ceased
  • 2023-08-30 CN CN202380065543.9A patent/CN119866230A/zh active Pending
  • 2023-08-30 JP JP2024546840A patent/JPWO2024057929A1/ja active Pending

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